Journal article
The impact of flow-induced forces on the morphogenesis of the outflow tract
Frontiers in physiology, v 5, pp 225-225
17 Jun 2014
PMID: 24987377
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
One percent of infants are born with congenital heart disease (CHD), which commonly involves outflow tract (OFT) defects. These infants often require complex surgeries, which are associated with long term adverse remodeling effects, and receive replacement valves with limited strength, biocompatibility, and growth capability. To address these problematic issues, researchers have carried out investigations in valve development and valve mechanics. A longstanding hypothesis is that flow-induced forces regulate fibrous valve development, however, the specific mechanisms behind this mechanotransduction remain unclear. The purpose of this study was to implement an
in vitro
system of outflow tract development to test the response of embryonic OFT tissues to fluid flow. A dynamic, three-dimensional bioreactor system was used to culture embryonic OFT tissue under different levels of flow as well as the absence of flow. In the absence of flow, OFT tissues took on a more primitive phenotype that is characteristic of early OFT cushion development where widely dispersed mesenchymal cells are surrounded by a sparse, disorganized extracellular matrix (ECM). Whereas OFT tissues subjected to physiologically matched flow formed compact mounds of cells, initated, fibrous ECM development, while prolonged supraphysiological flow resulted in abnormal tissue remodeling. This study indicates that both the timing and magnitude of flow alter cellular processes that determine if OFT precursor tissue undergoes normal or pathological development. Specifically, these experiments showed that flow-generated forces regulate the deposition and localization of fibrous ECM proteins, indicating that mechanosensitive signaling pathways are capable of driving pathological OFT development if flows are not ideal.
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Details
- Title
- The impact of flow-induced forces on the morphogenesis of the outflow tract
- Creators
- Stefanie V. Biechler - University of South CarolinaLorain Junor - University of South CarolinaAshlie N. Evans - University of South CarolinaJohn F. Eberth - University of South CarolinaRobert L. Price - University of South CarolinaJay D. Potts - University of South CarolinaMichael J. Yost - University of South CarolinaRichard L. Goodwin - University of South Carolina
- Publication Details
- Frontiers in physiology, v 5, pp 225-225
- Publisher
- Frontiers Media S.A
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000347062100003
- Scopus ID
- 2-s2.0-84904444333
- Other Identifier
- 991021902596404721
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- Web of Science research areas
- Physiology